Protective effect of dihydromyricetin on LPS-induced acute lung injury

Abstract

Dihydromyricetin (DHM), a bioactive flavonoid component isolated from Ampelopsis grossedentata, is known to have anti-inflammatory effect, but the effect of DHM on acute lung injury (ALI) is largely unknown. Here, we investigated the effect of DHM on ALI and the underlying mechanism by bioinformatic analyses and animal experiments. We found that pretreatment with DHM ameliorated lung pathological changes and suppressed the inflammation response in lung tissues after LPS challenge. The potential targets of DHM were predicted by DDI-CPI and DRAR-CPI tools and analyzed using the STRING server to predict the functionally related signaling pathways, such as MAPK signaling. Molecular docking calculations indicated that DHM could be embedded tightly into the binding pocket of ERK, JNK, and p38. Furthermore, the activation of MAPK signaling induced by LPS was inhibited by DHM. In conclusion, these findings suggest that DHM may exert its protective effect on ALI by inhibiting MAPK signaling. The present study supports a potential clinical application for DHM in treating ALI and provides a novel design that combines in silico methods with in vivo experiments for drug research.

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“…It was reported that DHM ameliorated lung pathological changes and lung edema in ALI mice challenged by LPS or CLP, which was associated with its inhibition of secretion of inflammatory cytokines TNF-α, IL1-β, IL-6 and IL-18. The responsible mechanism involved DHM activating PPAR-α expression as well as blocking the MAPK signaling pathway [ 167 ] and NLRP3 inflammasome [ 168 ]. Moreover, DHM had similar effects to 5 mg/kg DEX.…”

“…Moreover, DHM had similar effects to 5 mg/kg DEX. However, DEX inhibited Smad4 expression but DHM had no effect [ 167 ].…”

Mechanism of Dihydromyricetin on Inflammatory Diseases

“…Furthermore, DHM reduced inflammatory response via the JNK pathway in acute liver injury mice ( Wang et al, 2018a ). DHM reversed the metabolic syndrome by upregulating insulin receptor substrate-1 (IRS-1) (y612) tyrosine phosphorylation and improving insulin resistance in obese mice ( He et al, 2019 ).…”

Dihydromyricetin Acts as a Potential Redox Balance Mediator in Cancer Chemoprevention

“…Mediators of Inflammation Mediators of Inflammation factor NF-κB, and prostaglandin-E2 that regulate the inflammatory responses. Numerous studies reported that DHM showed anti-inflammatory activity through different molecular mechanisms such as suppression of proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), activation of the production of an anti-inflammatory cytokine (IL-10), inhibition of MAPKs, suppression of the production of prostaglandins and nitric oxide, and inhibition of the transcription factor NF-κB [3,4,79,80]. The inflammatory response of the brain or the spinal cord is known as neuroinflammation, and it has an important role in the development of depression by producing cytokines, chemokines, and ROS [26].…”